Effect Of XBP1 Deficiency In Cartilage On The Regulatory Network Of LncRNA/circRNA-miRNA-mRNA.
Ontology highlight
ABSTRACT:
SUBMITTER: Li X
PROVIDER: S-EPMC8692151 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:Accumulating evidence has indicated that noncoding RNAs are involved in intervertebral disc degeneration (IDD); however, the competing endogenous RNA (ceRNA)?mediated regulatory mechanisms in IDD remain rarely reported. The present study aimed to comprehensively investigate the alterations in expression levels of circular RNA (circRNA), long noncoding RNA (lncRNA), microRNA (miRNA/miR) and mRNA in the nucleus pulposus (NP) of patients with IDD. In addition, crucial lncRNA/circRNA?miRNA?mRNA ceRNA interaction axes were screened using the GSE67567 microarray dataset obtained from the Gene Expression Omnibus database. After data preprocessing, differentially expressed circRNAs (DECs), lncRNAs (DELs), miRNAs (DEMs) or genes (DEGs) between IDD and normal controls were identified using the Linear Models for Microarray data method. A protein?protein interaction (PPI) network was constructed for DEGs based on protein databases, followed by module analysis. The ceRNA network was constructed based on the interaction between miRNAs and mRNAs, and lncRNAs/circRNAs and miRNAs. The underlying functions of mRNAs were predicted using the Database for Annotation, Visualization and Integrated Discovery database. The present study identified 636 DECs, 115 DELs, 84 DEMs and 1,040 DEGs between patients with IDD and control individuals. PPI network analysis demonstrated that Fos proto?oncogene, AP?1 transcription factor subunit (FOS), mitogen?activated protein kinase 1 (MAPK1), hypoxia inducible factor 1 subunit ? (HIF1A) and transforming growth factor ?1 (TGFB1) were hub genes and enriched in modules. Metastasis?associated lung adenocarcinoma transcript 1 (MALAT1)/hsa_circRNA_102348?hsa??miR?185?5p?TGFB1/FOS, MALAT1?hsa?miR?155?5p?HIF1A, hsa_circRNA_102399?hsa?miR?302a?3p?HIF1A, MALAT1?hsa??miR?519d?3p?MAPK1 and hsa_circRNA_100086?hsa?miR?509?3p?MAPK1 ceRNA axes were obtained by constructing the ceRNA networks. In conclusion, these identified ceRNA interaction axes may be crucial targets for the treatment of IDD.
| S-EPMC6755180 | biostudies-literature
Project description:BackgroundThe high morbidity and mortality of colorectal cancer (CRC) have posed great threats to human health. Circular RNA (CircRNA) and microRNA (miRNA), acting as competing endogenous RNAs (ceRNAs), have been found to play vital roles in carcinogenesis. However, the biological function of ceRNAs in CRC pathogenesis and prognosis remains largely unexplored.AimTo identify the CRC-specific circRNA-miRNA-mRNA regulatory network and uncover the subnetwork associated with its prognosis.MethodsCircRNAs, miRNAs and mRNAs differentially expressed (DE) in CRC tissues were selected by expression file analysis in the Gene Expression Omnibus (GEO) database, and the downstream target molecules of circRNAs and miRNAs were predicted. Then, the intersection of differentially expressed RNA molecules with the predicted targets was determined to obtain a ceRNA network. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses were conducted to elucidate the possible mechanism of pathogenesis. A survival analysis using the gene profiles and clinical information in The Cancer Genome Atlas (TCGA) database was performed to identify the mRNAs associated with the clinical outcome of CRC patients and construct a prognostic subnetwork.ResultsWe downloaded three datasets (GSE126095, GSE41655 and GSE41657) of large-scale CRC samples from the GEO database. There were 55 DEcircRNAs, 114 DEmiRNAs and 267 DEmRNAs in CRC tissues compared with normal tissues. After intersecting these molecules with predicted targets, 19 circRNAs, 13 miRNAs and 28 mRNAs were chosen to develop a circRNA-miRNA-mRNA network. GO and KEGG functional enrichment analyses indicated that the retinol metabolic process, leukocyte chemotaxis, extracellular matrix remodeling, endoplasmic reticulum stress, alcohol dehydrogenase activity, gastric acid secretion, nitrogen metabolism and NOD-like receptor signaling pathway might participate in the tumorigenesis of CRC. After verifying the identified mRNA effect in the TCGA database, we finally recognized 3 mRNAs (CA2, ITLN1 and LRRC19) that were significantly associated with the overall survival of CRC patients and constructed a ceRNA subnetwork including 5 circRNAs (hsa_circ_0080210, hsa_circ_0007158, hsa_circ_0000375, hsa_circ_0018909 and hsa_circ_0011536) and 3 miRNAs (hsa-miR-601, hsa-miR-671-5p and hsa-miR-765), which could contain innovative and noninvasive indicators for the early screening and prognostic prediction of CRC.ConclusionWe proposed a circRNA-miRNA-mRNA regulatory network closely associated with the progression and clinical outcome of CRC that might include promising biomarkers for carcinogenesis and therapeutic targets.
| S-EPMC8223824 | biostudies-literature
Project description:The growing evidence suggests that circular RNAs (circRNAs) have significant associations with tumor occurrence and progression, yet the regulatory mechanism of circRNAs in lung adenocarcinoma (LUAD) remains unclear. This study clarified the potentially regulatory network and functional mechanism of circRNAs in LUAD. The expression data of circRNAs, microRNAs (miRNAs), and messenger RNAs (mRNAs) were obtained from the Gene Expression Omnibus (GEO) database. Relying on GSE101586, GSE101684, and GSE112214, we identified differentially expressed circRNAs (DEcircRNAs). Depending on GSE135918 and GSE32863, we screened out differentially expressed miRNAs (DEmiRNAs) and mRNAs (DEmRNAs), respectively. Then, a novel competing endogenous RNA (ceRNA) regulatory network related to LUAD was constructed. We also revealed biological processes and signal pathways regulated by these DEcircRNAs. Based on gene expression data and survival information of LUAD patients in The Cancer Genome Atlas (TCGA) and GEO, we implemented survival analysis to select DEmRNAs related to prognosis and build a novel circRNA-miRNA-mRNA hub regulatory network. Meanwhile, quantitative real-time PCR (qRT-PCR) was utilized to validate DEcircRNAs in the ceRNA hub regulatory network. As a result, a total of 8 DEcircRNAs, 19 DEmiRNAs, and 85 DEmRNAs were identified. The novel ceRNA regulatory network included 5 circRNAs, 8 miRNAs, and 22 mRNAs. The final ceRNA hub regulatory network contained two circRNAs, two miRNAs, and two mRNAs. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses indicated that the five DEcircRNAs may affect LUAD onset and progression through Wnt signaling pathway and Hippo signaling pathway. All in all, this study revealed the regulatory network and functional mechanism of circRNA-related ceRNAs in LUAD.
| S-EPMC8292838 | biostudies-literature
Project description:Circular RNA (circRNA) abnormal expression and regulation are involved in the occurrence and development of a variety of tumors. However, the role of circRNAs still remains unknown in gastrointestinal stromal tumors (GISTs). In the present study, the differential circRNA expression profile of GISTs was screened by human circRNAs chip and verified by qRT-PCR. The circRNA-miRNA-mRNA regulatory network was constructed using the cytoHubba plugin based on the Cytoscape software. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were performed to explore circRNA functions. Six significantly differential circRNAs were also verified in 20 pairs of GISTs and adjacent tissues by qRT-PCR. The result showed that a total of 543 differentially expressed circRNAs were identified in GISTs, of which 242 were up-regulated and 301 were down-regulated. Additionally, the circRNA-miRNA-mRNA network contained six circRNAs, 30 miRNAs, and 308 mRNAs, and the targeted mRNAs were associated with "regulation of biological process," "intracellular organelle," "protein binding," and enriched in Wnt signaling pathway. Furthermore, qRT-PCR demonstrated that hsa_circRNA_061346, hsa_circRNA_103114, and hsa_circRNA_103870 were significantly up-regulated in GISTs (n = 20), and hsa_ circRNA_405324, hsa_circRNA_406821, and hsa_circRNA_000361 were dramatically down-regulated in GISTs (n = 20). In addition, all of these circRNAs were shown to have high diagnostic values, and most of them were significantly associated with tumor size, mitotic figure, and malignant degrees in GISTs (P < 0.05). Therefore, we concluded that circRNAs were abnormally expressed in GISTs, and the circRNA-miRNA-mRNA regulatory network plays an important role in the occurrence and development of GISTs. Also, the identified six candidate circRNAs might be critical circRNAs and may present as potential diagnostic biomarkers for GISTs.
| S-EPMC7271966 | biostudies-literature
Project description:BackgroundAccumulating evidence supports the importance of noncoding RNAs and exosomes in coronary heart disease (CHD). However, exosomal-associated competing endogenous RNA- (ceRNA-) mediated regulatory mechanisms in CHD are largely unexplored. The present study aimed to explore exosomal-associated ceRNA networks in CHD.MethodsData from 6 CHD patients and 32 normal controls were downloaded from the ExoRBase database. CHD and normal controls were compared by screening differentially expressed mRNAs (DEMs), lncRNAs (DELs), and circRNAs (DECs) in serum exosomes. MicroRNAs (miRNAs) targeting DEMs were predicted using the Targetscan and miRanda databases, and miRNAs targeted by DELs and DECs were predicted using the miRcode and starBase databases, respectively. The biological functions and related signaling pathways of DEMs were analyzed using the David and KOBAS databases. Subsequently, a protein-protein interaction (PPI) network was established to screen out on which hub genes enrichment analyses should be performed, and a ceRNA network (lncRNA/circRNA-miRNA-mRNA) was constructed to elucidate ceRNA axes in CHD.ResultsA total of 312 DEMs, 43 DELs, and 85 DECs were identified between CHD patients and normal controls. Functional enrichment analysis showed that DEMs were significantly enriched in "chromatin silencing at rDNA," "telomere organization," and "negative regulation of gene expression, epigenetic." PPI network analysis showed that 25 hub DEMs were closely related to CHD, of which ubiquitin C (UBC) was the most important. Hub genes were mainly enriched in "cellular protein metabolic process" functions. The exosomal-associated ceRNA regulatory network incorporated 48 DEMs, 73 predicted miRNAs, 10 DELs, and 15 DECs. The LncRNA/circRNA-miRNA-mRNA interaction axes (RPL7AP11/hsa-miR-17-5p/UBC and RPL7AP11/hsa-miR-20b-5p/UBC) were obtained from the network.ConclusionsOur findings provide a novel perspective on the potential role of exosomal-associated ceRNA network regulation of the pathogenesis of CHD.
| S-EPMC8249161 | biostudies-literature
Project description:Aimwe aimed to construct a bioinformatics-based co-regulatory network of mRNAs and non coding RNAs (ncRNAs), which is implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD), followed by its validation in a NAFLD animal model.Materials and methodsThe mRNAs-miRNAs-lncRNAs regulatory network involved in NAFLD was retrieved and constructed utilizing bioinformatics tools. Then, we validated this network using an NAFLD animal model, high sucrose and high fat diet (HSHF)-fed rats. Finally, the expression level of the network players was assessed in the liver tissues using reverse transcriptase real-time polymerase chain reaction.Resultsin-silico constructed network revealed six mRNAs (YAP1, FOXA2, AMOTL2, TEAD2, SMAD4 and NF2), two miRNAs (miR-650 and miR-1205), and two lncRNAs (RPARP-AS1 and SRD5A3-AS1) that play important roles as a co-regulatory network in NAFLD pathogenesis. Moreover, the expression level of these constructed network-players was significantly different between NAFLD and normal control. Conclusion and future perspectives: this study provides new insight into the molecular mechanism of NAFLD pathogenesis and valuable clues for the potential use of the constructed RNA network in effective diagnostic or management strategies of NAFLD.
| S-EPMC8269036 | biostudies-literature
Project description:Long non-coding RNAs (lncRNAs) are ncRNA transcripts >200 nucleotides that are important genetic regulators. LncRNAs can directly regulate mRNA through a lncRNA-mRNA regulatory mode and can also regulate mRNA through competitive binding to micro (mi)RNA, which is generally known as the competitive endogenous RNA (ceRNA) network. The present study evaluated the functional roles and regulatory networks of lncRNAs in chronic glomerulonephritis (CGN). The proliferative ability of mouse glomerular mesangial cells (GMCs) induced by different concentrations of lipopolysaccharide (LPS) was assessed using the Cell Counting Kit-8 assay, and RNA sequencing (RNA-seq) was performed to identify differentially expressed lncRNAs in LPS-induced GMCs. Based on the sequencing results, six lncRNAs were selected for validation using reverse transcription-quantitative PCR (RT-qPCR). Furthermore, the lncRNA-mRNA regulatory network and the lncRNA-miRNA-mRNA ceRNA network were constructed to assess the role and mechanism of CGN-related lncRNAs. To elucidate the biological functions of lncRNAs, Gene Ontology (GO) biological process term enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were performed on all mRNAs involved in the lncRNA-mRNA regulatory network and in the ceRNA network. A total of 1,532 differentially expressed lncRNAs, including 594 upregulated lncRNAs and 938 downregulated lncRNAs, were identified using RNA-seq. The results of RT-qPCR validation were consistent with RNA-seq results. An lncRNA-mRNA regulatory network, including 236 lncRNAs and 556 mRNAs, and a ceRNA network, including 6 lncRNAs, 18 miRNAs and 419 mRNAs, were successfully constructed. The GO biological process term enrichment and KEGG pathway enrichment analyses demonstrated that those lncRNAs were often related to inflammatory response and substance metabolism. The present study identified key CGN-related lncRNAs in LPS-induced GMCs, and further demonstrated a global view of the lncRNA-mRNA regulatory network and ceRNA network involved in CGN. These results offered novel insights into the roles of lncRNAs in the pathogenesis of CGN and identified potential diagnostic biomarkers.
| S-EPMC10375445 | biostudies-literature
Project description:Osteoarthritis (OA) is a joint disease that is pervasive in life, and the incidence and mortality of OA are increasing, causing many adverse effects on people's life. Therefore, it is very vital to identify new biomarkers and therapeutic targets in the clinical diagnosis and treatment of OA. ncRNA is a nonprotein-coding RNA that does not translate into proteins but participates in protein translation. At the RNA level, it can perform biological functions. Many studies have found that miRNA, lncRNA, and circRNA are closely related to the course of OA and play important regulatory roles in transcription, post-transcription, and post-translation, which can be used as biological targets for the prevention, diagnosis, and treatment of OA. In this review, we summarized and described the various roles of different types of miRNA, lncRNA, and circRNA in OA, the roles of different lncRNA/circRNA-miRNA-mRNA axis in OA, and the possible prospects of these ncRNAs in clinical application.
| S-EPMC8714905 | biostudies-literature
Project description:Background Circular RNAs (circRNAs) are described as endogenous non-coding RNAs that have been reported to play important roles in the development and progression of cancers. This study aimed to reveal the circRNA-related regulatory mechanism in esophageal squamous cell carcinoma (ESCC). Methods A genome-wide circRNA microarray assay was performed to profile the expression of circRNAs in the blood of preoperative ESCC patients and healthy controls. A systematic method of data mining was performed to identify the differentially expressed miRNAs (DEmiRs) and differentially expressed genes (DEGs) based on the metaMA and RankProd analysis. Bioinformatics analyses and multiple tools were employed to construct the potential circRNA–miRNA–mRNA regulatory network. Results Thirty-three differentially expressed circRNAs were identified in the ESCC blood, including 31 downregulated and two upregulated circRNAs in the blood of ESCC patients compared with the healthy controls. Twenty-three DEmiRs and 2,220 DEGs were obtained by the integration of microarray datasets. An ESCC-associated circRNA–miRNA–mRNA network was constructed based on 31 circRNAs, 3 DEmiRs, and 190 DEGs. Enrichment analyses indicated that the DEGs were associated with a series of biological processes and cancer-related pathways. The protein–protein interaction (PPI) network was generated by the 190 DEGs, with 10 hub genes verified in the network. Subsequently, a sub-network was established for ESCC, which included 29 circRNAs, 2 miRNAs, and 10 hub genes. Conclusion Our study provided a novel clue to help understand the circRNA–miRNA–mRNA regulatory mechanism, highlighting the potential roles of circRNAs in the pathogenesis and development of ESCC.
| S-EPMC7966720 | biostudies-literature
Project description:BackgroundStroke is the leading cause of death and disability worldwide, with ischemic stroke (IS) being the most prevalent type. Circular RNAs (circRNAs) are involved in the pathological process of IS and are promising biomarkers for the diagnosis of IS. However, studies focusing on circRNAs acting as microRNAs (miRNAs) sponges in regulating mRNA expression are currently scarce.MethodsIn this study, expression profiles of circRNAs (GSE195442), miRNAs (GSE117064), and mRNAs (GSE58294) from the Gene Expression Omnibus (GEO) database were analyzed. Differentially expressed circRNAs (DEcircRNAs), differentially expressed miRNAs (DEmiRNAs), and differentially expressed mRNAs (DEmRNAs) were identified by R software. The target miRNAs and target genes were predicted by several bioinformatics methods. Then, we performed Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis of the DEmRNAs. Subsequently, the protein-protein interaction (PPI) network and the competing endogenous RNA (ceRNA) regulatory network were visualized by Cytoscape software. Finally, we further constructed an immune-related circRNA-miRNA-mRNA regulatory sub-network in IS.ResultsA total of 35 DEcircRNAs, 141 DEmiRNAs, and 356 DEmRNAs were identified. By comprehensive analysis of bioinformatics methods, we constructed a circRNA-miRNA-mRNA regulatory network, including 15 DEcircRNAs, eight DEmiRNAs, and 39 DEmRNAs. FGF9 was identified as an immune-related hub gene. Immune cell analysis indicated a significantly higher level of neutrophils in IS, and the expression of FGF9 was significantly negatively correlated with the level of neutrophils. Eventually, miR-767-5p was predicted as the upstream molecules of FGF9, and circ_0127785 and circ_0075008 were predicted as the upstream circRNAs of miR-767-5p.ConclusionOur study provides novel insights into the molecular mechanisms governing the progression of IS from the perspective of immune-related ceRNA networks.
| S-EPMC9240315 | biostudies-literature